Author Interviews, Breast Cancer, Nature / 10.11.2018

MedicalResearch.com Interview with: "Mammogram" by slgckgc is licensed under CC BY 2.0Prof. Cathrin Brisken MD, PhD ISREC, School of Life Sciences Ecole Polytechnique Fédérale (EPFL) CH-1015 Lausanne, Switzerland  MedicalResearch.com: What is the background for this study? Response: Estrogen receptor signaling has been well characterized in various in vitro models, like breast cancer cell lines.  Understanding estrogen receptor action in complex in vivo context is much more challenging. We obtained elegant mouse models in which either all estrogen receptor function or specifically either the hormone dependent (AF-2) or the hormone independent (AF-1) function were ablated. Using the mammary glands from these mice we performed tissue recombination studies to discern the role of the different aspects of estrogen receptor signaling in the mouse mammary epithelium and its different cell populations. (more…)
Author Interviews, Lung Cancer, Nature, NYU, Technology / 17.09.2018

MedicalResearch.com Interview with: Aristotelis Tsirigos, Ph.D. Associate Professor of Pathology Director, Applied Bioinformatics Laboratories New York University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pathologists routinely examine slides made from tumor samples to diagnose cancer types. We studied whether an AI algorithm can achieve the same task with high accuracy. Indeed, we show that such an algorithm can achieve an accuracy of ~97%, slightly better than individual pathologists. In addition, we demonstrated that AI can be used to predict genes that are mutated in these tumors, a task that pathologists cannot do. Although the accuracy for some genes is as high as 86%, there is still room for improvement. This will come from collecting more training data and also from improvement in the annotations of the slides by expert pathologists.   (more…)
Author Interviews, Biomarkers, Cancer Research, Immunotherapy, Melanoma, Nature / 11.09.2018

MedicalResearch.com Interview with: Dr. Noam Auslander PhD National Cancer institute and the Center for Bioinformatics and Computational Biology University of Maryland, College Park MedicalResearch.com: What is the background for this study? Response: Immunotherapy – specifically immune checkpoint blockage (ICB) therapy – has been shown to be very effective in treating melanoma. However, only some patients with advanced tumors currently benefit from ICB therapies, while others are completely resistant and hence can be spared from the associated side effects and costs. Hence, predicting which patients are most likely to respond is an important challenge that can have great clinical benefits.   (more…)
Author Interviews, Mental Health Research, Nature, University of Pennsylvania / 08.08.2018

MedicalResearch.com Interview with: MedicalResearch.com Interview with: Dr. Theodore Satterthwaite MD Assistant professor in the department of Psychiatry, and Cedric Xia, a MD-PhD candidate Perelman School of Medicine at the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: Unlike other branches of modern medicine, psychiatry still solely replies on patient reports and physician observations for clinical decision-making. Without biologically-based tests, the diagnostic categories for mental health do not carve nature at its joint. This is evident in the high levels of co-morbidity across disorders and heterogeneity within disorders. Through this research, we studied a large sample of adolescents who completed MRI-based functional imaging, and used recently-developed machine learning techniques to uncover specific abnormalities that are highly predictive of a wide variety of psychiatric symptoms. Essentially, we tried to find brain patterns that were predictive of different types of psychiatric symptoms. We discovered four such brain-guided dimensions of psychopathology: mood, psychosis, fear, and disruptive behavior. While each of these dimensions exhibits a unique pattern of brain connectivity, a common feature of brain anomaly is shared across the dimensions. Notably, in all linked dimensions, the default mode network and fronto-parietal network, two brain regions that usually become increasingly distinct as the brain matures, were abnormally connected. This loss of normal brain network segregation supports the hypothesis that many psychiatric illnesses may be disorders of brain development. MedicalResearch.com: What should readers take away from your report? Response: This study shows that we can start to use the brain to guide our understanding of psychiatric disorders in a way that’s fundamentally different than grouping symptoms into clinical diagnostic categories. By moving away from clinical labels developed decades ago, we can begin to let the biology speak for itself. Our ultimate hope is that understanding the biology of mental illnesses will allow us to develop better treatments for our patients. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: This study demonstrates the importance of incorporating vast amounts of biological data to study mental illness across clinical diagnostic boundaries. Moving forward, we hope to integrate genomic data in order to describe pathways from genes to brain to symptoms, which could ultimately be the basis for novel treatments for mental illness. MedicalResearch.com: Is there anything else you would like to add? Response: Future breakthroughs in brain science to understand mental illness requires large amount of data. While the current study takes advantage of one of the largest samples of youth, the size (n=999) remains dwarfed by the complexity of the brain. The neuroscience community is actively working towards collecting higher quality data in even larger samples, so we can validate and build upon the findings. Citation: Cedric Huchuan Xia, Zongming Ma, Rastko Ciric, Shi Gu, Richard F. Betzel, Antonia N. Kaczkurkin, Monica E. Calkins, Philip A. Cook, Angel García de la Garza, Simon N. Vandekar, Zaixu Cui, Tyler M. Moore, David R. Roalf, Kosha Ruparel, Daniel H. Wolf, Christos Davatzikos, Ruben C. Gur, Raquel E. Gur, Russell T. Shinohara, Danielle S. Bassett, Theodore D. Satterthwaite. Linked dimensions of psychopathology and connectivity in functional brain networks. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-05317-y [wysija_form id="3"] [last-modified] The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.Dr. Theodore Satterthwaite MD Assistant professor in the department of Psychiatry, and Cedric Xia, a MD-PhD candidate Perelman School of Medicine at the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Unlike other branches of modern medicine, psychiatry still solely replies on patient reports and physician observations for clinical decision-making. Without biologically-based tests, the diagnostic categories for mental health do not carve nature at its joint. This is evident in the high levels of co-morbidity across disorders and heterogeneity within disorders. Through this research, we studied a large sample of adolescents who completed MRI-based functional imaging, and used recently-developed machine learning techniques to uncover specific abnormalities that are highly predictive of a wide variety of psychiatric symptoms. Essentially, we tried to find brain patterns that were predictive of different types of psychiatric symptoms. We discovered four such brain-guided dimensions of psychopathology: mood, psychosis, fear, and disruptive behavior. While each of these dimensions exhibits a unique pattern of brain connectivity, a common feature of brain anomaly is shared across the dimensions. Notably, in all linked dimensions, the default mode network and fronto-parietal network, two brain regions that usually become increasingly distinct as the brain matures, were abnormally connected. This loss of normal brain network segregation supports the hypothesis that many psychiatric illnesses may be disorders of brain development. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, Nature / 23.07.2018

MedicalResearch.com Interview with: Luca Magnani, Ph.D CRUK Fellow/Senior Research Fellow Department of Surgery and Cancer Imperial Centre for Translational and Experimental Medicine Room 140 1st floor ICTEM building Imperial College Hammersmith London, UK MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by the Yin Yang1 molecule? Response: This study was designed to investigate the evidence of non-genetic mechanisms that could contribute to breast cancer biology. Specifically, we developed a map of regulatory regions from luminal breast cancer patients. Regulatory regions are pieces of DNA that are not transcribed into protein-coding genes but they provide information about where and how much each gene should be activated. It is worth highlighting that cancer is not only the consequence of gene mutations but also the result of the wrong genes expressed at the wrong time.  To catalogue regulatory regions we looked for specific modifications that are strongly associated with their activity (epigenetic modifications). Doing so we developed the first extensive catalogue  of non-coding DNA regions that might play an essential role in regulating how breast cancer cell behaves. Regulatory regions do their job by interacting with specific molecules called transcription factors. These molecules can read the information stored in these regulatory regions and contribute to regulate gene expression. Yin Yang 1 is one of such molecules and was previously thought as a ambiguous player capable of activating or repressing gene activity.   (more…)
Author Interviews, Cancer Research, Genetic Research, Nature, Prostate Cancer / 13.06.2018

MedicalResearch.com Interview with: Fredrick R. Schumacher, PhD, MPH. Associate Professor, Department of Population & Quantitative Health Sciences Case Western Reserve University Cleveland MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Our study examines the genetic underpinnings of prostate cancer initiation using technology to test variants across the genome. Our study focused on men of European ancestry and included over 80,000 men with prostate cancer and 60,000 men without disease. We discovered 63 novel genetic variants associated with prostate cancer risk, which increases our knowledge of prostate cancer genetic risk factors by more than 60%. A genetic risk score created from the combination of 163 new and known prostate cancer risk variants revealed men with the highest genetic risk score are nearly seven times more likely to develop disease compared to the average man. Additionally, men with the lowest genetic risk score have a 85% risk reduction of developing prostate cancer compared to the average. Lastly, these new discoveries uncover several biological mechanisms involved in the initiation of prostate cancer. (more…)
Author Interviews, Fertility, Nature / 09.06.2018

MedicalResearch.com Interview with: Tomer Avidor-Reiss, Ph.D.  Professor, College of Natural Sciences and Mathematics Department of Biological Sciences University of Toledo Toledo, OH 43606 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Most dividing cells in the body need exactly two centrioles for normal cell division and development. Abnormalities in centriole number can cause cancer and devastating developmental defects. Because of this importance of centriole number and because all cells originate from the zygote – the product of the sperm and egg – it makes sense that the zygote should possess two centrioles, as well. However, the egg does not contain any centrioles, so the sperm is the sole contributor of the centrioles; and yet, it is currently thought that the sperm contains only one centriole. This is problematic because supposedly that leaves the zygote with only one centriole, even though it must propagate cells with two centrioles. In the past, we found that insect sperm have an atypical centriole that escaped discovery because it is so different. We therefore hypothesized that humans may also have an atypical sperm centriole. Our new paper shows that in human sperm there exists, in addition to the known centriole, a second centriole that deviates from the typical structural and composition that is expected from a centriole. Although it looks very different from any centriole ever described, we found that it functions in an in vitro functional assay. Furthermore, during fertilization, it performs the functions traditionally associated with centrioles. Together, this resolves a 50-year-long debate regarding the centrioles of human sperm; the sperm contains two functional centrioles, despite that one is atypical.  (more…)
Author Interviews, Cancer Research, Leukemia, Nature, University of Pennsylvania / 01.06.2018

MedicalResearch.com Interview with: Dr. J Joseph Melenhorst, PhD Director, Product Development & Correlative Sciences laboratories (PDCS) Adjunct Associate Professor Penn Medicine Center for Cellular Immunotherapies University of Pennsylvania MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by CLL and CAR T cells?  Response: We started treating patients with a form of blood cancer called CLL (chronic lymphocytic leukemia) using a form of gene therapy wherein we engineer the patient’s own immune cells – T cells – with a tumor targeting molecule: The CAR, which stands for chimeric antigen receptor. When we engineer the patient’s immune cells we use a vehicle, in this case virus, that inserts the payload – the CAR – into the patient’s DNA. The virus disappears, and the CAR stays. Where this CAR inserts itself is unpredictable, but we always get stably engineered cells.  (more…)
Author Interviews, Infections, Nature, NIH, PLoS, Rheumatology / 16.04.2018

MedicalResearch.com Interview with: John B. Harley, MD, PhD Professor and Director David Glass Endowed Chair Center for Autoimmune Genomics and Etiology (CAGE) Department of Pediatrics University of Cincinnati Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio 45229 MedicalResearch.com: What is the background for this study? Response: Previous work has shown that Epstein-Barr virus infection is associated with systemic lupus erythematosus and studies of the origins of the autoimmune response have also suggested that the autoimmunity of this disease may originate with the immune response against this virus. In the meantime, many investigators have been studying the genetics of lupus over the past 25 years. They have found about 100 convincing genes that alter the risk of developing lupus. (more…)
Author Interviews, Blood Pressure - Hypertension, Nature / 06.04.2018

MedicalResearch.com Interview with: Dr. Charles Brenner, PhD Chief Scientific Advisor ChromaDex MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nicotinamide adenine dinucleotide (NAD) is the central regulator of metabolism. NAD is under attack in multiple conditions of metabolic stress and declines in human aging. Thus, using supplements to maintain NAD has emerged as an important strategy to support healthy aging. There are three vitamin precursors of NAD. However, two of those forms (niacin and nicotinamide) have unwanted side effects and/or inhibit some of the metabolic regulators that can be stimulated by higher NAD. Nicotinamide riboside (NR) is the most recently discovered NAD precursor vitamin. Research has shown that NR boosts NAD more than the other precursors, doesn’t cause flushing, doesn’t inhibit sirtuin enzymes, and that the pathway that converts NR to NAD is turned on in tissues undergoing stress and damage. Commercialized as NIAGEN®, NR has been clinically proven to significantly increase NAD levels in people as an oral supplement. NIAGEN® is the only NR with published human safety, efficacy and tolerability studies. The University of Colorado study is the first clinical trial showing that not only does NIAGEN® boost NAD levels, it also may have a beneficial effect on cardiovascular health and function. (more…)
Author Interviews, Genetic Research, Nature, OBGYNE, UCLA / 22.03.2018

MedicalResearch.com Interview with: Marlena Fejzo, PhD Aassociate researche David Geffen School of Medicine UCLA.  MedicalResearch.com: What is the background for this study? Response: Most women experience some nausea and vomiting of pregnancy, and the worst 2% are diagnosed with Hyperemesis Gravidarum which is associated with poor maternal and fetal outcomes. I had HG in 2 pregnancies. In my second pregnancy my HG was so severe that I could not move without vomiting and did not keep any food or water down for 10 weeks. I was put on a feeding tube, but ultimately lost the baby in the second trimester. I am a medical scientist by training so I looked into what was known about HG. At the time, very little was known, so I decided to study it. I partnered with the Hyperemesis Education and Research Foundation (HER) and we did a survey on family history of .Hyperemesis Gravidarum that provided evidence to support a role for genes. I collected saliva samples from HG patients and their unaffected acquaintances to do a DNA study. Then I partnered with the personal genetics company, 23andMe to do a genome scan and validation study, which identified 2 genes, GDF15 and IGFBP7, linked to HG. (more…)
Aging, Author Interviews, Nature / 07.02.2018

MedicalResearch.com Interview with: Douglas P. Kiel, MD, MPH Professor of Medicine Harvard Medical School Director Musculoskeletal Research Center Institute for Aging Research, Hebrew SeniorLife Associate Member Broad Institute of Harvard and MIT  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Why we age? and how we age?, are perennial questions that are of interest to all. The research described in this publication brings together two major and different concepts of aging - epigenetic aging, which is manifested by modifications on DNA and telomere-related aging, which is manifested by shortening of chromosome ends (telomeres).  In our search for genes that could potentially affect epigenetic aging, we detected  a variant of the TERT gene (whose encoded protein, telomerase maintains telomere length) to be associated with accelerated epigenetic aging. TERT is a subunit of the enzyme telomerase which is a widely known enzyme for the following reasons: 1)    Telomerase has been touted as an anti-aging enzyme. It has been called a modern fountain of youth. However, some scientists have pointed out that it is unlikely to become a source of anti-aging therapies (see the review article by de Magalhães JP1, Toussaint in Rejuvenation Research (2004) .https://www.ncbi.nlm.nih.gov/pubmed/15312299)   Our new results gained by the epigenetic clock also indicate that telomerase will not halt organismal aging. 2)    The book "The Telomere Effect" by Nobel prize winner Elizabeth Blackburn and Elissa Epel was on the New York Times best seller list and received substantial news coverage:https://www.cbsnews.com/news/telomere-effect-book-living-younger-healthier-longer/ Our data provides a much needed  understanding of the molecular drivers of the epigenetic clock and reveal a unexpected and paradoxical connection between two seemingly distinct aging clocks: the telomere clock and the epigenetic clock. Our main finding was that variants in the human telomerase reverse transcriptase gene (TERT) were associated with increased “intrinsic epigenetic aging.”  (more…)
Author Interviews, Nature, Technology / 02.02.2018

MedicalResearch.com Interview with: Dr. Sarav Rajan, PhD Scientist Antibody Discovery and Protein Engineering MedImmune MedicalResearch.com: What is the background for this study? What are the main findings? Response: During an infection, B cells (a type of white blood cell) create antibodies against antigens present on a pathogen. These cells can be extremely rare, and finding them among the millions of other cells is extremely challenging. Existing methods to examine B cells require a trade-off: either capture the full sequence repertoire by next-generation sequencing but functionally screen just a subset, or culture a subset of B cells and fully screen them. Instead, our method captures the complete repertoire within a typical blood draw and screens all its members to identify the rare antigen-positive antibodies. Using a new microfluidic approach, we recovered the antibody genes from one million B cells encapsulated in picoliter-scale droplets, breaking through a widely-published view that amplifying from single cells in such small volumes is inefficient. The resulting library seamlessly integrates into our high-throughput screening infrastructure to enable rapid isolation of desired antibodies. Using this method, we were able to isolate a panel of rare cross-reactive antibodies targeting influenza. (more…)
Author Interviews, Flu - Influenza, Nature, Vaccine Studies / 26.01.2018

MedicalResearch.com Interview with: “Syringe and Vaccine” by NIAID is licensed under CC BY 2.0Dr. Lei Deng PhD Postdoctoral researcher Institute for Biomedical Sciences at Georgia State University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Influenza A viruses evade human herd immunity by genetic hypervariation. Annual influenza epidemics are estimated to cause about 3 to 5 million cases of severe illness, and about 290,000 to 650,000 deaths. Vaccination is still the most effective way to prevent diseases, but current influenza vaccines provide limited protections against mismatched circulating virus strains. This drives scientists to develop universal influenza vaccines that can induce broad immune responses against all influenza A virus infections. We used biochemistry and nanotechnology to generate a double-layered protein nanoparticle universal influenza vaccine. The layered nanoparticle contains genetically modified influenza virus components without irrelevant carry/structural proteins and chemicals and confers strong and long-lasting immunity in laboratory mice against H1N1, H3N2, H5N1 and H7N9 infections. We also explain the protection mechanism of antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP) play the main role in the immune protection.  (more…)
Author Interviews, Autism, Nature / 20.01.2018

MedicalResearch.com Interview with: Di Wu, Msc PhD candidate at Indiana University Graduate Research Assistant Department of Physics Indiana University Bloomington Linked-in: www.linkedin.com/in/di-wu-3a197373  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Current clinical diagnosis and evaluations of Autism Spectrum Disorder (ASD). has remained subjective in nature. There is a need to have objective assessments for the disorder. We discovered in this study an important motion feature that was unknown before. This feature provides a clear screening of ASD. It gave a remarkable quantitative connection between the way children with ASD move and their psychiatric scores, like the IQ score and the Vineland Adaptive Behavior Scale. This connection we captured suggests that the motor feature may be an essential core feature characterizing ASD deficits, as well as neurodevelopment in general. (more…)
Author Interviews, Biomarkers, Melanoma, Nature / 17.01.2018

MedicalResearch.com Interview with: Daniel S. Peeper, PhD Professor of Functional Oncogenomics (VUmc) Member of Oncode Institute Head, Division of Molecular Oncology & Immunology Chair, Scientific Faculty Council Chair, Translational Research Board The Netherlands Cancer Institute Amsterdam The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: BRAF mutant melanomas are now commonly treated with either immunotherapy or with the combination of BRAFi + MEKi. Recent clinical trials showed that combination checkpoint blockade gives 58% 3 year survival for advanced melanoma. For BRAF+MEKi these numbers are somewhat less impressive. Our study relates to the latter setting. Clearly, most patients treated with this combination do not experience a durable clinical benefit. We showed previously that resistance to these inhibitors is commonly associated with a striking increase in the number of AXL+ cells; this is the rationale for the current study.  (more…)
Author Interviews, Baylor College of Medicine Houston, C. difficile, Nature / 05.01.2018

MedicalResearch.com Interview with: Professor Robert Britton PhD Therapeutic Microbiology Laboratory Department of Molecular Virology and Microbiology Alkek Center for Metagenomics and Microbiome Research Baylor College of Medicine MedicalResearch.com Interview: How would you summarise your findings? Response: As a brief summary of our work, certain strains of Clostridium difficile have emerged in the past 20 years that have resulted in epidemics worldwide, leading to C. difficile becoming one of the most common causes of hospital acquired infections.  Two ribotypes of C. difficile, RT027 and RT078, emerged as key epidemic ribotypes associated with increased disease prevalence and increased mortality in patients.  We found that both of these ribotypes have acquired the ability to consume the disaccharide trehalose by two completely independent mechanisms.  We further show that trehalose enhances disease severity of C. difficile infection in a manner that requires C. difficile to metabolize trehalose in mice.  We also show that trehalose is present in the distal intestine of mice and humans in concentrations that the RT027 ribotype can metabolize.  Because RT027 and RT078 strains were present in clinics at least 10-20 years prior to their becoming epidemic isolates, we looked where people would acquire trehalose in the diet. In 2000 the FDA approved trehalose for human consumption (EFSA did so in 2001) and based on the GRAS report from the FDA the amount of trehalose predicted to be consumed once released on the market would vastly increase what people get naturally from the diet.  Our data support that these two ribotypes increased in prevalence due to a change in the human diet. (more…)
Aging, Author Interviews, Blood Pressure - Hypertension, Nature, UT Southwestern / 27.12.2017

MedicalResearch.com Interview with: Hamid Mirzaei, Ph.D. Assistant Professor of Biochemistry University of Texas Southwestern Department of Biochemistry Dallas, TX 75390 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Aging is a complex process at the cellular level with distinct organismal phenotypes. Despite millennia-old obsession with aging and relentless pursuits for ways to stop and reverse it, such elixir has not been found due to the complexity of the involved mechanisms and our limited understanding of the processes that lead to aging. Although progress has been made in recent years in slowing down the aging process in model organisms and human cells. In this study, we report that and FDA approved antihypertensive drug, hydralazine, decelerates aging in C. elegans by mechanisms that seem to resemble dietary restriction. We show that hydralazine increases the median lifespan of the C. elegans by 25% which is comparable to or better than other known antiaging compounds. We demonstrate that not only hydralazine-treated worms live longer, they appear to be healthier in general. Because aging is directly linked to neurodegenerative diseases, we tested our drug on both in vitro and in vivo models of neurodegenerative diseases using chemical and biological stressors (rotenone and tau fibrils) and show that hydralazine has neuroprotective properties as well. (more…)
Author Interviews, Autism, Genetic Research, Nature / 12.11.2017

MedicalResearch.com Interview with: Woo-Yang Kim, Ph.D Associate Professor Department of Developmental Neuroscience Munroe-Meyer Institute University of Nebraska Medical Center Omaha, NE 68198-5960 MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions. Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown. Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes. Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Genetic Research, Nature / 07.11.2017

MedicalResearch.com Interview with: Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer's disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer's patients than in human controls of the same age; and it is lower in the elderly with respect to young adults. Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho. (more…)
Author Interviews, Mental Health Research, Nature / 30.10.2017

MedicalResearch.com Interview with: Hyun Ji Noh PhD Computational Scientist, Medical and Population Genetics Broad Institute of MIT and Harvard MedicalResearch.com: What is the background for this study? What are the main findings? Response: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder, characterized by intrusive thoughts and repetitive behaviors. OCD is estimated to affect roughly 80 million people worldwide, but its neurobiology remains poorly understood. To understand the disorder’s underpinnings, we searched for genetic mutations that are associated with OCD. For this, we first identified 608 genes that were most likely to be important  in OCD - some that have previously been identified in OCD-like behaviors in dogs and mice, and others in human autism, which also involves repetitive behaviors. We compared these genes in 592 people with OCD and 560 people without OCD, and found that 4 of these genes were significantly different between people with and without OCD: NRXN1, HTR2A, CTTNBP2 and REEP3. All of these four genes have important functions in the brain. Specifically, we found that the variants in NRXN1 are likely to change its ability to bind other synaptic proteins. Synaptic proteins link neurons together, and are critical for transmitting signals through the brain. We also found that the variants in CTTNBP2 and REEP3 don’t actually change the proteins made by these genes, but instead probably affect gene regulation (for example, how much of the protein is made). These ‘regulatory’ variants disrupt the binding of transcription factors (proteins that regulate expression of genes in the body) near the gene. (more…)
Author Interviews, Nature, Weight Research / 17.10.2017

MedicalResearch.com Interview with: Dr. Hoon-Ki Sung MD PhD Scientist at The Hospital for Sick Children (SickKids) and Assistant Professor in Laboratory Medicine & Pathobiology University of Toronto  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Despite extensive research and medical interventions, the prevalence of obesity and associated metabolic disease is increasing. More and more studies show that obesity and its associated metabolic problems are often associated with unhealthy lifestyles and eating habits, including frequent eating (non-stop) throughout the day, resulting in a shorter period of physiological fasting. As such, various dietary approaches, such as calorie restriction and intermittent fasting have gained popularity as therapeutic strategies for obesity treatment. Intermittent-fasting is when one temporarily stops eating for a period of time, returns to normal food consumption, and then temporarily stops again. In our study we examined the effect of an intermittent-fasting regimen, without restricting caloric intake, in mice. We found that an intermittent fasting regimen not only prevented obesity in mice, but also improved metabolism by changing the quality of fat in the body. Our findings show that the health of the mice is significantly influenced by daily eating patterns. The addition of a 'stop eating' period converted inflammatory fat to brown-like (or beige) fat by anti-inflammatory immune cells, meaning it changed bad fat into good fat. The results are exciting, because they show that weight loss is not the sole benefit of fasting. Fasting also restores the dual function of fat cells, which is to store energy and to release energy. (more…)
Author Interviews, Diabetes, Nature / 04.10.2017

MedicalResearch.com Interview with: Andrew F. Stewart MD Irene and Dr. Arthur M. Fishberg Professor of Medicine Director, Diabetes, Obesity and Metabolism Institute Institute at the Icahn School of Medicine at Mount Sinai New York, NY 10029 MedicalResearch.com: What is the background for this study? Response: Diabetes results ultimately from an inadequate number of insulin-producing “beta” cell in the pancreas.  Ideally, these would regenerate when they are lost or damaged, but unfortunately inducing them to regenerate or proliferate has proven impossible until recently. In 2015 and others we identified the first class of drugs – the harmine analogues - that are able to induce human beta cells to proliferate.  In this study, we wanted to identify additional pathways that can lead to human beta cell proliferation at higher rates than we had been able to induce with harmine.   For this we turned to a rare type of benign (i.e., not malignant, not cancer) tumor of the beta cells in the pancreas called “insulinomas”. These tiny tumors overproduce insulin and cause hypoglycemia (low blood glucose) which in turn causes seizures, loss of consciousness and confusion.  Once they are discovered, then can easily be removed via laparoscopic surgery, and the person is cured.  Since they are so rare, and since they are benign and easily cured, insulinomas have not been included in large genome sequencing studies of patients wit cancer.  However, we reasoned that they must hold the genomic recipe or wiring diagram for inducing human beta cells to replicate, so we perfumed next-generation DNA and RNA sequencing on a large series (38) of insulinomas. (more…)
Author Interviews, Nature, OBGYNE, Pediatrics, Toxin Research / 05.09.2017

MedicalResearch.com Interview with: Ashley Larsen, PhD Assistant professor Bren School of Environmental Science & Management University of California, Santa Barbara MedicalResearch.com: What is the background for this study? What are the main findings? Response: The relationship between pesticides and adverse birth outcomes has been recognized as an important question for quite some time, and there have been many good studies on the topic. Since randomly exposing people to different levels of pesticides is clearly unethical, researchers focused on the health consequences of non-occupational pesticide exposure often have to choose between detailed studies that follow a couple hundred or couple thousand individuals through pregnancy or larger scale studies that use easier to observe, but less accurate metrics of pesticide exposure (e.g. nearby crops or crop types). Here we tried to provide complementary insight by bridging the gap between detail and scale using detailed pesticide use data and individual birth certificate records for hundreds of thousands of births in an agriculturally dominated region of California. While we found negative effects of pesticide use on birth outcomes including low birth weight, preterm birth and birth abnormalities, these effects were generally in the magnitude of a 5-9% increase in probability of an adverse outcome, and only observed for individuals exposed to very high levels of pesticides. (more…)
Author Interviews, Cancer Research, Gastrointestinal Disease, Infections, Nature, Stem Cells / 20.08.2017

MedicalResearch.com Interview with: Michael Sigal PhD Clinical scientist of the Charité -- Universitätsmedizin Berlin Investigator at the Max Planck Institute for Infection Biology  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have previously found that H. pylori can colonize gastric glands and that in colonized glands the epithelial turnover was increased. We wanted to characterize the mechanisms that control the gland turnover in the stomach. We found that Axin2, a classic Wnt target gene, marks two different subpopulations of cells with stem cell properties, one of which is Lgr5-positive and the other one Lgr5-negative. Both populations are affected by Rspondin 3, that is produced in myofibroblasts right beneath the stem cell compartment. Rspondin is crucial for stem cell signaling and knockout of Rspondin 3 in myofibroblasts results in loss of Lgr5 and Axin2 expression. Once we increased the bioavailability of Rspondin, that now could also interact with cells outside of the stem cell compartment, we noticed that the number of Axin2 positive stem cells dramatically increased. Of interest, only Lgr5-negative cells expanded in number and proliferate more, while the Lgr5-positive cells remained silenced. Infection with Helicobacter pylori leads to an expansion of Axin2-positive cells which is driven by increased expression of Rspondin3. Expansion of the long lived stem cell pool could be an explanation for how H. pylori infection increases the risk for gastric cancer. (more…)
Author Interviews, Genetic Research, Nature / 29.07.2017

MedicalResearch.com Interview with: Dr. Zoltán Kutalik, PhD Group Leader Swiss Institute of Bioinformatics Assistant professor at the Institute of Social and Preventive Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Why do some of us live longer than others? While the environment in which we live – including our socio-economic status or the food we eat – plays the biggest part, about 20 to 30% of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity. Until now, the most comprehensive studies had found only two hits in the genome. (more…)
Aging, Author Interviews, McGill, Nature / 29.06.2017

MedicalResearch.com Interview with: Pr. Siegfried Hekimi PhD McGill University MedicalResearch.com: What is the background for this study? What are the main findings? Response: We analyzed data about the longest living individuals over the period of time during which the record can be trusted. We found that there was no detectable plateauing of the maximum possible lifespan. This is consistent with not clearly observed plateau in the currently increasing average lifespan as well. (more…)
Author Interviews, Genetic Research, Nature, Scripps / 21.06.2017

MedicalResearch.com Interview with: Michael Farzan PhD Co-chair and Professor Department of Immunology and Microbiology Florida Campus The Scripps Research Institute Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Response: CRISPR is system for immune protection of bacteria.  It has now been widely adopted for use in editing mammalian cells.  The most commonly used CRISPR effector protein is Cas9.  Cas9 binds a guide RNA to recognize a DNA target, for example an incoming virus infecting a bacterium, or a gene in a human chromosome.  In bacteria, Cas9 requires a second protein to clear the guide RNA from a longer "CRISPR array", basically a string of guide RNAs. We have been studying a CRISPR effector protein related to Cas9 called Cpf1.  In bacteria it was know that, unlike Cas9, Cpf1 could cleave a CRISPR array by itself, without assistance from a second protein.  We knew that if it could do the same thing in human cells, it would help to simplify a number of gene-editing applications.  We were able to show that Cas9 could indeed excise multiple guide RNAs from a single message RNA in human cells.  We further showed that this approach was more efficient than the previous ways that guide RNAs were generated for gene editing, even more so when multiple guide RNAs were needed. (more…)
Author Interviews, Autism, Mineral Metabolism, Nature, Pediatrics / 05.06.2017

MedicalResearch.com Interview with: Manish Arora, PhD Associate Professor Environmental Medicine & Public Health Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? What are the main findings? Response: Autism has both genetic and environmental risk factors. Our aim was to study if exposure to toxic metals, such as lead, or disruptions in the uptake of essential nutrient elements such as manganese or zinc would be related to autism risk. Furthermore, we were interested in not only understanding how much exposure had taken place but also which developmental periods were associated with increased susceptibility to autism risk. Researchers suspect that the risk factors for autism start early in life, even prenatally, but measuring in utero exposures is technically very challenging. We used a newly developed technique that uses lasers to map growth rings in baby teeth (like growth rings in trees) to reconstruct the history of toxic metal and essential nutrient uptake. We applied this technology in samples collected from twins, including twins who were discordant for autism. This allowed us to have some control over genetic factors. We found that twins with autism had higher levels of lead in their teeth compared to their unaffected twin siblings. They also had lower levels of zinc and manganese. The lower uptake of zinc was restricted to approximately 10 weeks before birth to a few weeks after birth, indicating that as a critical developmental period. (more…)